RT Journal Article
SR Electronic
T1 Expression profiling of early mitogen responsive genes and their potential roles in tumor progression: modeling the plasminogen activation cascade.
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 51
OP 51
VO 65
IS 9 Supplement
A1 Qi, Li
A1 Higgins, Paul J.
YR 2005
UL http://cancerres.aacrjournals.org/content/65/9_Supplement/51.2.abstract
AB Proc Amer Assoc Cancer Res, Volume 46, 2005 219 Induced transit of growth-arrested cells into the proliferative cycle is associated with certain regenerative and pathophysiological processes and is a critical event in tumor progression. Defining the mechanisms of transcriptome activation and cell cycle transit may define new molecular targets for cancer treatment. Microarray profiling and real-time PCR were used to position growth state-dependent activation of the plasminogen activator inhibitor type 1 (PAI-1) gene within the context of the global transcriptional response of pre-malignant human keratinocytes (HaCaT cells) to serum growth factor stimulation. Serum growth factors were added to growth-arrested HaCaT cells and mRNA isolated two hours later for transcriptome activation analysis. Flow cytometry of acridine orange-stained cells indicated that at this early time point cells were still residing in a substate kinetically equivalent to G0. The identified changes in gene expression, therefore, were initiated prior to entrance into a cycling G1 condition. By gene clustering studies we identified unique patterns of gene activation for proliferation, migration and invasion. The PAI-1 gene, together with other plasminogen system components (uPA, uPAR), is transiently and highly expressed during the early onset of cell cycle entry. The involvement of wound healing and matrix remodeling genes is consistent with changing anchorage-requirements attendant to the acquisition of a mitogenic or invasive phenotype. Through functional genomics, our preliminary data not only are in good correlation with biochemical characterization of known genes but also provide opportunities to identify new molecular targets focusing on transcriptome activation, cell cycle progression, and growth-state dependency. Supported by NIH grant GM 57242.